Alpha Consumable Cartridges with complex flow geometry for: lyophilized and liquid reagents, 2 rotary valves, 2 high speed thermocycling chambers, 2 fluidic interfaces, with a submillimeter imaging channel.

Microfluidic-Based POC Device for Detection and Analysis of HIV Directly From Blood

Gener8 | March 6, 2023

Microfluidic-Based POC Device for Detection and Analysis of HIV Directly From Blood

Client/Summary

Chipcare, a biotech company specializing in multiplexed Point-of-Care (POC) diagnostics for sexually transmitted infections, approached Gener8 to develop a turnkey sample-to-answer POC device and microfluidic-based cartridge for analyzing blood from HIV patients. The goal was to create a diagnostic device that would allow healthcare providers to perform rapid tests and provide earlier therapy. However, developing a consumable cartridge and an instrument that would work together seamlessly presented significant challenges.

 

The Challenges

The primary challenge for the microfluidic consumable was to design a vertically oriented fluidic cartridge that could perform multiple PCR-based assays on a single platform while storing both liquid and lyophilized reagents onboard. The detection channel required microfluidic dimensions of 20 µm diameter to enable sensitive fluorescent detection. Due to the low volumes of liquid moving through narrow channels, the tolerances for the cartridge were very tight, with virtually no low dead volumes. Additionally, the team faced the challenge of designing a single-source syringe pump that could drive the rotary valves without causing foaming.

On the instrument side, the challenge was to develop a device that could interface with the disposable cartridge, creating a commercial POC medical device. The prototype instrument included two reagent connectors, heat lysis and thermocycling modules, variable parameter rotary valves, air displacement pumps, solenoid-driven magnetic lever arms, and multiple wavelength laser diodes and optics for fluorescent detection and imaging. When connected to the consumable cartridge, the instrument could perform heated sample lysis, amplification, and detection. Aligning the design and development of each component was critical to delivering a functional and cost-effective product that met the client's requirements.

With any project consisting of a consumable and an instrument, it’s essential to align the design and development of each in order to deliver a functional and cost-effective product that meets the client’s requirements.

Methods Employed

The Consumable

To close the channels, polycarbonate films were laser welded onto the polycarbonate cartridge. To prevent bubbles and isolate the instrument, hydrophobic vents were added. A low-cost, compact form factor was achieved by automating a 27-step workflow with rotary valves. Liquid and dried reagent packs were heat-sealed, followed by leak testing to ensure quality control.

Top view of CAD for PCR cartridge.

Isometric view of CAD for PCR cartridge.

Back view of CAD for PCR cartridge.

The Instrument

Gener8 enhanced the customer's optical imaging and detection platform by improving reliability and image quality while reducing its overall size. This was achieved by carefully re-designing the optical train. Gener8 also automated the consumable cartridge interface, including the actuation of rotary valves, magnetic bead capture, high-speed thermal cycling, heat lysis, and fluidic control of lyophilized and liquid reagents to achieve the desired chemistry. Custom electronics and specialized controls were developed to enable these complex medical assays, adding significant value to the platform.

Image of an early Prototype/Alpha platform to demonstrate interaction with a complex molded consumable cartridge.

CAD Image of improved optical assembly for fluorescent detection and imaging.

CAD of Primary Cartridge interface assembly with high speed thermocycler, fluidic interfaces, rotary valves, magnetic bead capture mechanisms, and imaging location.

Alpha Consumable Cartridges with complex flow geometry for: lyophilized and liquid reagents, 2 rotary valves, 2 high speed thermocycling chambers, 2 fluidic interfaces, with a submillimeter imaging channel.

Rotary valve port locations. Starting position indexed to 0; Intermediary between the 2 immediately adjacent ports. Locations are numbered clockwise from the starting position with spacing based on the included RV sketch.

The Solution

Gener8 fulfilled Chipcare's demand for a user-friendly and entirely integrated instrument and consumable for their POC applications. We demonstrated the functionality of all cartridge interfaces, including high-speed thermocycling with less than 3 degrees Celsius per second heating and cooling at the sample, and successful optical detection and imaging in a submillimeter imaging channel within the consumable cartridge. We carried out assay development using the prototype and alpha platforms, which were developed in close collaboration with Chipcare. The necessary sensitivity required for precise detection was obtained due to the low dead volume and tight manufacturing tolerances necessary for the assay.

Expertise Employed

The Consumable

  • Microfluidics design and testing
  • Computational fluid dynamics
  • High-volume consumable development
  • Mold flow analysis
  • Laser welding

The Instrument

  • Holistic mechanical and system design
  • Fluidics design and testing
  • Optical and optomechanical development and design
  • Thermal simulation and testing
  • Electronics design
  • Embedded firmware engineering
  • Design for manufacturability

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